Multivalent Presentation of Mannose on Hyperbranched Polyglycerol and their Interaction with Concanavalin A Lectin

• Published in: Chembiochem : a European journal of chemical biology 2011-05, Vol.12 (7), p.1075-1083
• Main Authors: Papp, Ilona, Dernedde, Jens, Enders, Sven, Riese, Sebastian B., Shiao, Tze Chieh, Roy, René, Haag, Rainer
• Format: Article
• Language: English
• Subjects: click chemistry; Con A lectin; Concanavalin A - chemistry; Concanavalin A - metabolism; Glycerol - chemistry; Glycerol - metabolism; glycopolymers; glycosylation; Mannose - analogs & derivatives; Mannose - chemical synthesis; Mannose - chemistry; Mannose - metabolism; Molecular Structure; multivalency; Polymers - chemistry; Polymers - metabolism; Surface Plasmon Resonance
• ISSN: 1439-4227; 1439-7633
• DOI: 10.1002/cbic.201000718

We describe the synthesis of multivalent mannose derivatives by using hyperbranched polyglycerols (hPG) as a scaffold with different linker structures. Grafting of protected mannose (Man) units is achieved by using CuI‐catalyzed Huisgen click chemistry with either an anomeric azide or propargyl ether onto complementarily functionalized alkyne or azido polymer surfaces. NMR spectroscopy, dynamic light scattering (DLS), IR spectroscopy, size‐exclusion chromatography (SEC), and elemental analysis have been used to characterize the hPG–Man compounds. The surface availability and bioactivity of Man‐modified polymers were evaluated by using a competitive surface plasmon resonance (SPR)‐based binding assay by interactions of the glycopolymers with concanavalin A (Con A), a lectin that binds mannose containing molecules. The results indicated that the novel glycoarchitectures presented in this work are efficient inhibitors of Con A–mannose recognition and resulted in inhibitor concentrations (mean IC50) from the micro‐ to the nanomolar range, whereas the corresponding monovalent mannoside (methyl‐Man) requires millimolar concentrations. The results provide an interesting structure–activity relationship for libraries of materials that differ in the linkage of the sugar moiety presented on a biocompatible polyglycerol scaffold. Architecture‐dependent binding: Multivalent dendritic glycoconjugates with high binding affinities for Con A were efficiently prepared, and a detailed structure–activity relationship study revealed the best linker and the degree of functionalization for the Man–polymer conjugates.